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Publication : Non-coding RNA Generated following Lariat Debranching Mediates Targeting of AID to DNA.

First Author  Zheng S Year  2015
Journal  Cell Volume  161
Issue  4 Pages  762-73
PubMed ID  25957684 Mgi Jnum  J:223318
Mgi Id  MGI:5648667 Doi  10.1016/j.cell.2015.03.020
Citation  Zheng S, et al. (2015) Non-coding RNA Generated following Lariat Debranching Mediates Targeting of AID to DNA. Cell 161(4):762-73
abstractText  Transcription through immunoglobulin switch (S) regions is essential for class switch recombination (CSR), but no molecular function of the transcripts has been described. Likewise, recruitment of activation-induced cytidine deaminase (AID) to S regions is critical for CSR; however, the underlying mechanism has not been fully elucidated. Here, we demonstrate that intronic switch RNA acts in trans to target AID to S region DNA. AID binds directly to switch RNA through G-quadruplexes formed by the RNA molecules. Disruption of this interaction by mutation of a key residue in the putative RNA-binding domain of AID impairs recruitment of AID to S region DNA, thereby abolishing CSR. Additionally, inhibition of RNA lariat processing leads to loss of AID localization to S regions and compromises CSR; both defects can be rescued by exogenous expression of switch transcripts in a sequence-specific manner. These studies uncover an RNA-mediated mechanism of targeting AID to DNA.
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